Article

Paraproteinemic Renal Diseases that Involve the Tubulo-Interstitium

Department of Pathology, St. Louis University, St. Louis, Mo., USA.
Contributions to nephrology (Impact Factor: 1.53). 02/2007; 153:105-15. DOI: 10.1159/000096763
Source: PubMed

ABSTRACT The renal response to deposition of monoclonal light chains represents a spectrum of pathologic changes that can be divided into glomerular or tubulo-interstitial processes. Involvement of the tubulo-interstitium can include activation of the proximal tubule, proximal tubule injury/cell death, and cast nephropathy. In these diseases, the culprit is not the intact immunoglobulin protein but instead the immunoglobulin light chain. Recent noninvasive tests, including immunofixation electrophoresis or quantification of serum free light chains, have increased the sensitivity for detection of an abnormality in circulating free light chains and are invaluable ancillary tools, but short of renal biopsy, the diagnosis of these diseases can prove challenging. A description of the pathobiology and overview of the approach to management of these light chain-mediated renal lesions is provided.

Download full-text

Full-text

Available from: Paul W Sanders, Jun 22, 2015
0 Followers
 · 
176 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function.
    BioMed Research International 04/2014; 2014:167125. DOI:10.1155/2014/167125 · 2.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mononoclonal gammopathies are not unfrequent in people over 50 years old (3,2 %). At presentation about half of them are classified as MGUS (monoclonal gammopathy of undetermined significance) whereas only 25 % have clinically documented plasma cell dyscrasias (myeloma, Waldenström macroglobulinemia or amyloidosis). MGUS has a 1 % per year risk of progression to such plasma cell malignant disorders. Establishing the diagnosis of monoclonal gammopathy requires immunofixation of serum and urine. Serum free light chain (fFLC) assay is a recently available test for diagnosis and monitoring patients with those plasma cell dyscrasias. The used antisera are specific for hidden épitopes on light chains bound to the heavy chain in the intact immunoglobulin, but exposed on the free light chains. Abnormal calculated serum κ/λ ratio is assumed to give information on large monoclonal production excess. In clinical context with absence or minimal monoclonal immunoglobulin marker, such as light chain multiple myeloma, non-secretory multiple myeloma, amyloidosis and light chain deposition disease, fFLC has proven to be a useful laboratory test. For the more frequent plasma cell dyscrasias (multiple myeloma with intact immunoglobulin, MGUS) the clinical utility of the fFLC for diagnosis and monitoring needs more extensive prospective studies to be established.
    Revue Francophone des Laboratoires 08/2008; 2008(404):37–50. DOI:10.1016/S1773-035X(08)71559-4
  • [Show abstract] [Hide abstract]
    ABSTRACT: We assessed efficacy, safety, and reversal of renal impairment (RI) in untreated patients with multiple myeloma given bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide (VMPT-VT) maintenance or bortezomib-melphalan-prednisone (VMP). Exclusion criteria included serum creatinine ≥ 2.5 mg/dL. In the VMPT-VT/VMP arms, severe RI (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min), moderate RI (eGFR 31-50 mL/min), and normal renal function (eGFR > 50 mL/min), were 6%/7.9%, 24.1%/24.9%, and 69.8%/67.2%, respectively. Statistically significant improvements in overall response rates and progression-free survival were observed in VMPT-VT versus VMP arms across renal cohorts, except in severe RI patients. In the VMPT group, severe RI reduced overall survival (OS). RI was reversed in 16/63 (25.4%) patients receiving VMPT-VT versus 31/77 (40.3%) receiving VMP. Multivariate analysis showed male sex (P = .022) and moderate RI (P = .003) significantly predicted RI recovery. VMP patients achieving renal response showed longer OS. In both arms, greater rates of severe hematologic adverse events were associated with RI (eGFR < 50 mL/min), however, therapy discontinuation rates were unaffected. VMPT-VT was superior to VMP for cases with normal renal function and moderate RI, whereas VMPT-VT failed to outperform VMP in patients with severe RI, although the relatively low number of cases analyzed preclude drawing definitive conclusions. VMPT-VT had no advantage in terms of RI reversal over VMP.
    Blood 09/2011; 118(22):5759-66. DOI:10.1182/blood-2011-05-353995 · 9.78 Impact Factor